Figure 3

The complex role of the PLAU-PLAUR pathway in the airways. PLAUR is a complex, multi-domain (D1, 2, 3) molecule and exists as a membrane bound GPI linked protein and in multiple soluble forms. The interaction between PLAU-PLAUR is critical for the conversion of plasminogen to plasmin and is regulated by a series of proteins including; PAI-1, PAI-2 and SERPINE2 which have previously been implicated in COPD pathogenesis [16, 31]. Plasmin has many downstream proteolytic effects including those common to remodelling of the airways e.g. MMP activation. In addition PLAUR interacts with several membrane receptors leading to the activation of signalling cascades resulting in alterations in; proliferation, migration, adhesion, endocytosis and cytoskeletal changes. PLAUR also exists in multiple soluble forms (sPLAUR) generated by splicing and/or proteolytic cleavage implicated in chemotaxis and interactions with the extracellular matrix [5, 35, 36].